Ganetespib in Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor-resistant Non-small Cell Lung Cancer

Eisuke Kurihara, Kazuhiko Shien, Hidejiro Torigoe, Tatsuaki Takeda, Yuta Takahashi, Yusuke Ogoshi, Takahiro Yoshioka, Kei Namba, Hiroki Sato, Ken Suzawa, Hiromasa Yamamoto, Junichi Sou, Mikio Okazaki, Tadahiko Shien, Shuta Tomida, Shinichi Toyooka

Research output: Contribution to journalArticle

Abstract

BACKGROUND: The 90-kDa heat-shock protein (HSP90) is a chaperone protein expressed at high levels in cancer cells and is involved in the folding or stabilization of several client proteins, including epidermal growth factor receptor (EGFR). Ganetespib is a second-generation HSP90 inhibitor with a potent antitumor effect against various cancer types. MATERIALS AND METHODS: This study examined the antitumor effect of ganetespib in EGFR-mutant non-small cell lung cancer (NSCLC) cells and experimentally established EGFR-tyrosine kinase inhibitor (TKI)-resistant cells harboring various resistance mechanisms, including EGFR T790M mutation, met proto-oncogene amplification, and epithelial-mesenchymal transition. RESULTS: Ganetespib showed a potent antitumor effect at low concentrations, suppressing EGFR-related downstream pathway molecules and inducing cleavage of poly ADP-ribose polymerase in all examined EGFR-TKI-resistant cell lines in vitro. Ganetespib also inhibited in vivo tumor growth in resistant cells harboring EGFR T790M. CONCLUSION: Ganetespib might be a promising therapeutic option for the treatment of patients with EGFR-TKI-resistant NSCLC.

Original languageEnglish
Pages (from-to)1767-1775
Number of pages9
JournalAnticancer research
Volume39
Issue number4
DOIs
Publication statusPublished - Apr 1 2019

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Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Protein-Tyrosine Kinases
HSP90 Heat-Shock Proteins
Neoplasms
Epithelial-Mesenchymal Transition
Proto-Oncogenes
Poly(ADP-ribose) Polymerases
STA 9090
Proteins
Cell Line
Mutation
Therapeutics
Growth

Keywords

  • acquired drug resistance
  • EGFR-TKI
  • ganetespib
  • HSP90 inhibitor
  • non-small cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ganetespib in Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor-resistant Non-small Cell Lung Cancer. / Kurihara, Eisuke; Shien, Kazuhiko; Torigoe, Hidejiro; Takeda, Tatsuaki; Takahashi, Yuta; Ogoshi, Yusuke; Yoshioka, Takahiro; Namba, Kei; Sato, Hiroki; Suzawa, Ken; Yamamoto, Hiromasa; Sou, Junichi; Okazaki, Mikio; Shien, Tadahiko; Tomida, Shuta; Toyooka, Shinichi.

In: Anticancer research, Vol. 39, No. 4, 01.04.2019, p. 1767-1775.

Research output: Contribution to journalArticle

Kurihara, Eisuke ; Shien, Kazuhiko ; Torigoe, Hidejiro ; Takeda, Tatsuaki ; Takahashi, Yuta ; Ogoshi, Yusuke ; Yoshioka, Takahiro ; Namba, Kei ; Sato, Hiroki ; Suzawa, Ken ; Yamamoto, Hiromasa ; Sou, Junichi ; Okazaki, Mikio ; Shien, Tadahiko ; Tomida, Shuta ; Toyooka, Shinichi. / Ganetespib in Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor-resistant Non-small Cell Lung Cancer. In: Anticancer research. 2019 ; Vol. 39, No. 4. pp. 1767-1775.
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